The initial entry of lentivirus-infected monocytes into the brain and subsequent development of inflammatory foci are mediated by selective recruitment and activation of circulating monocytes. Previously, we have demonstrated upregulated VCAM-1 in brain in SIV/HIV encephalitis. The novel group of chemotactic cytokines, termed chemokines, has a pivotal role in leukocyte activation, including increased adhesion molecule expression, and in directed migration and stimulation of leukocyte effector functions. However, the role of chemokines in the pathogenesis of AIDS encephalitis has not been examined. We utilized the SIV/macaque model of AIDS to examine the role of chemokines in AIDS encephalitis. Brain tissue from 12 rhesus monkeys with histologically confirmed AIDS encephalitis was immunostained with monoclonal antibodies against MCP-1, MCP-2, MCP-3, MIP-1`, MIP-1 , RANTES, IL-8 and IP-10. These tissues were compared to those from uninfected (n=6) and SIV-infected (n=6) macaques without encephalitis. In animals with SIV encephalitis there was upregulation of MCP-3, MIP-1`, MIP-1 , RANTES, and IP-10 when compared to nonencephalitic animals. Chemokine expression correlated with monocytic infiltrates, VCAM-1 expression and viral loads in brain. Our data indicate that